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Nucleic Acids Res. 2014 Jan;42(Database issue):D231-9. doi: 10.1093/nar/gkt1253. Epub 2013 Dec 1.

eggNOG v4.0: nested orthology inference across 3686 organisms.

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European Molecular Biology Laboratory, Computational Biology Unit, Meyerhofstrasse 1, 69117 Heidelberg, Germany, University of Zurich and Swiss Institute of Bioinformatics, Institute of Molecular Life Sciences, Winterthurerstrasse 190, 8057 Zurich, Switzerland, Institute for Systems Biology, 401 Terry Avenue North, Seattle, WA 98109-5234, USA, Bioinformatics and Genomics Programme, Centre for Genomic Regulation (CRG), C/Dr. Aiguader 88, 08003 Barcelona, Spain, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain, CUBE-Division of Computational Systems Biology, Department of Microbiology and Ecosystem Science, University of Vienna, Althanstraße 14, 1090 Vienna, Austria, Institute of Biological, Environmental & Rural Sciences, Aberystwyth University, Penglais, Aberystwyth, Ceredigion, SY23 3FG, UK, Biotechnology Center, TU Dresden, 01062 Dresden, Germany, Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, 2200, Copenhagen N, Denmark and Max-Delbrück-Centre for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany.


With the increasing availability of various 'omics data, high-quality orthology assignment is crucial for evolutionary and functional genomics studies. We here present the fourth version of the eggNOG database (available at that derives nonsupervised orthologous groups (NOGs) from complete genomes, and then applies a comprehensive characterization and analysis pipeline to the resulting gene families. Compared with the previous version, we have more than tripled the underlying species set to cover 3686 organisms, keeping track with genome project completions while prioritizing the inclusion of high-quality genomes to minimize error propagation from incomplete proteome sets. Major technological advances include (i) a robust and scalable procedure for the identification and inclusion of high-quality genomes, (ii) provision of orthologous groups for 107 different taxonomic levels compared with 41 in eggNOGv3, (iii) identification and annotation of particularly closely related orthologous groups, facilitating analysis of related gene families, (iv) improvements of the clustering and functional annotation approach, (v) adoption of a revised tree building procedure based on the multiple alignments generated during the process and (vi) implementation of quality control procedures throughout the entire pipeline. As in previous versions, eggNOGv4 provides multiple sequence alignments and maximum-likelihood trees, as well as broad functional annotation. Users can access the complete database of orthologous groups via a web interface, as well as through bulk download.

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